The review article "Glutamate Neurotoxicity and Diseases of the Nervous System", Neuron, 623-34 (1988) summarizes the present state of knowledge of glutamate neurotoxicity, of the various effects of such toxicity and the various diseases involved. The article describes three kinds of glutamate receptors and summarizes known competitive and noncompetitive blockers of such receptors, providing also a variety of theories on the mechanisms of such activity. According to this article, considerable efforts are being focused on bringing an N-methyl-D-aspartate (NMDA) antagonist to bear on some of the diseases associated with glutamate neurotoxicity. Since no proven effective therapy for neuronal injury, or degeneration, is yet known, and, for example, stroke alone is one of the leading causes of death in many countries, the importance of finding such NMDA antagonist is self-evident. The article states that it will be important to determine whether certain NMDA antagonists are more effective--or have fewer side effects--than others in specific disease states.
Some of the compounds of general formula (I) are disclosed in U.S. Pat. Nos. 4,179,519 and 4,876,276. As disclosed in said U.S. patents, these essentially pure synthetic (+)--(3S,4S)-THC derivatives and analogues are devoid of any undesired cannabimimetic psychotropic side-effects. These known compounds have been described as having analgetic, antiemetic and antiglaucoma activity.
The inventors have now found that the said known compounds, as well as some novel compounds, in addition to having said analgetic, antiemetic and anti-glaucoma activity, are also effective against the diseases and conditions mentioned above, possibly as excitatory amino acid receptor blockers, for example NMDA- or glutamate-blockers or interaction with the glycine receptor, and are effective in the alleviation and treatment of many of the abnormal states involving said neurotransmitters toxicity.